Research and development of new products and techniques and quality control of existing products and techniques in many industries require the task of determining various characteristics, including for example dimensional characteristics, of particles a few millimeters or less in size. Typically, the particles are suspended in air or a liquid medium, and the size and shape of the particles vary greatly within a given sample of the suspension. For example, the various shapes may include substantially spherical, rod-shaped and plate-shaped particles to name a few. Thus, due to the disparity of particle sizes and shapes within a sample of the suspension, the size and shape characteristics of many, if not all, particles must be accessed to obtain a meaningful statistical representation of the actual size distribution of the particles in the suspension.
Conventional technologies for measuring the size of particles in a suspension include ensemble and non-ensemble technologies. In the so-called ensemble technology, signals from multiple particles are simultaneously detected and recorded as a single variable. Thereafter, an appropriate theoretical model is utilized to provide estimated size information inferred from the variable as recorded in various different experimental configurations. In such a technology, the determination of more than one parameter is difficult and generally cannot be accomplished, and size is typically represented as a single parameter, such as, a mean value or a distribution.
In a so-called non-ensemble technology, particles within a sample of the suspension are analyzed one at a time and a signal is detected from each individual particle. For instance, individual particles can be analyzed electronically based on the Coulter Principle in which size is determined by the change of electrical impedance measured while a particle passes between a pair of electrodes. Other examples of methods for analyzing the size of individual particles include optical methods using a single optical particle counter, aerodynamic methods in which time-of-flight is measured, and microscopic image analysis methods utilizing electronically or optically obtained images. Except for the image analysis method, the conventional non-ensemble technologies can be used only to provide a single size parameter, typically in the form of equivalent sphere diameter. In addition, many of the above referenced technologies produce a size parameter based strictly on the assumption that the shape of each particle within the suspension is a perfect sphere. Thus, any deviation of particle shape from that of a sphere produces errors or bias in the results of the particle size determination.
Most conventional techniques produce unsatisfactory results when analyzing the size distribution of particles that are non-spherical, particularly when at least some of the particles have extreme shapes such as rod-like or plate-like shapes. Thus, the determined size distribution often does not accurately reflect the actual size distribution of particles within a given sample of a suspension, and with respect to quality control issues, such techniques are not sufficiently sensitive to detect changes in the sizes and shapes of particles that may exist from one sample to the next. Further, a single size parameter utilized to represent sizes of particles in a sample clearly no longer meets the needs of current particle research, development, production and quality control. The conventional technology often uses a selected pre-defined size distribution or some other statistically calculated size distribution that does not reflect the actual size distribution of the particles.
Determining a true size distribution has become particularly critical in some industries, such as the pharmaceutical industry where the determination of size distribution utilizing dual parameters instead of a single parameter is preferred and desired. Traditional image analysis, referenced above, provides a two-dimensional analysis for each particle imaged in a fixed projection. However, the required particle orientation, sample preparation, time consumption, and expense of conventional microscopic technologies limit their application in daily research and development and quality control operations.
Examples of some known image analysis systems and systems for determining particle size distributions are disclosed in U.S. Pat. Nos.: 4,097,845 and 4,175,860 issued to Bacus; U.S. Pat. No. 4,338,024 issued to Bolz et al.; U.S. Pat. No. 4,538,299 issued to DeForest; U.S. Pat. No. 4,817,446 issued to Kanamori; U.S. Pat. No. 5,268,966 issued to Kasdan; U.S. Pat. No. 5,655,028 issued to Soll et al.; and U.S. Pat. No. 6,317,511 issued to Horiuchi. In addition, see U.S. patent application Ser. No. 09/677,076 which was filed on Sep. 29, 2000 and which is assigned to the assignee of the present application, and see the commercially available RapidVUE™ particle shape and size analyzer marketed by Beckman Coulter, Inc., Miami, Fla.
Although the aforementioned apparatus, methods, systems and techniques can function satisfactorily for their intended purposes, there exists a need for an apparatus and method which can accurately determine size distribution of particles within a sample of a suspension and which are capable of expressing the size distribution in a manner that readily conveys the information to an intended person. Preferably, the apparatus and method should rapidly measure and determine the shape and size of each individual particle within an image and should simultaneously display the information in real time. In addition, preferably the expression of the results should be presented to a viewer in a display enabling the viewer to quickly, if not substantially instantaneously, determine the actual distribution of particle shapes and sizes within the sample. The display unit can be a printer which prints the dimensional representation or a display screen. Further, preferably the apparatus and method should be capable of use in daily operations, should be cost effective, and should require only a minimum of skill to operate, utilize and maintain.
With the foregoing in mind, a primary object of the present invention is to provide an apparatus and method that accurately determine the actual shape and size of particles within a sample of a suspension.
Another object of the present invention is to provide an apparatus and method that are capable of expressing the actual shape and size distribution of the particles in a manner that readily conveys such information to an intended entity.
A further object of the present invention is to provide an apparatus and method that rapidly measure and determine the shape and size of each individual particle within an image and that simultaneously display the information in real time.
A still further object of the present invention is to provide an apparatus and method that provide a visual display to an intended viewer enabling the viewer to quickly, if not substantially instantaneously, determine the actual distribution of particle shapes and sizes within an analyzed sample.
Yet another object of the present invention is to provide an apparatus that is capable of use in daily operations in a cost efficient manner requiring only a minimum of skill to operate, utilize and maintain.